These infections sicken about 500,000 people a year, cause tens of thousands of deaths, and cost the U.S. health care system about $5 billion, according to investigators at the University of Pennsylvania.

C. difficile causes diarrhea, severe gut inflammation and can lead to deadly blood infections, especially in the elderly.

A review of nationwide health insurance data found a nearly 200 percent increase in the annual incidence of multiple recurring C. difficile infections between 2001 and 2012. For ordinary C. difficile, incidence rose by about 40 percent.

Patients with multiple recurring C. difficile infections tended to be older (average age 56 versus 49), female, and were more likely to have used antibiotics, corticosteroids or acid-reducing drugs, the findings showed.

The reasons for the rise in multiple recurring C. difficile cases remain unclear, but researchers said the findings highlight the need for new therapies.

The most promising new treatment is fecal microbiota transplantation. In the procedure, helpful gut bacteria are transferred to a patient's digestive tract to restore a balance that makes it easier to fight infection. While these stool transplants have shown promise in small studies, they have yet to be thoroughly evaluated, the study authors noted.

"The increasing incidence of C. difficile being treated with multiple courses of antibiotics signals rising demand for fecal microbiota transplantation in the United States," study senior author Dr. James Lewis said in a university news release.

Lewis is a professor of gastroenterology and senior scholar in the Center for Clinical Epidemiology and Biostatistics.

"While we know that fecal microbiota transplantation is generally safe and effective in the short term, we need to establish the long-term safety of this procedure," he added.

The report was published July 4 in the journal Annals of Internal Medicine.

More information

The U.S. Centers for Disease Control and Prevention has more on C. difficile.